NeuroanatomyAlpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease?
Section snippets
Subjects
Three- to 10-month-old, virgin male Fischer 344 (F344; n=42) and SpragueāDawley (SD; n=12) rats were purchased from Harlan (Indianapolis, IN, USA). Rats were housed individually and maintained on a 12-h light/dark schedule at 22ā24 Ā°C. Solid chow (laboratory diet No. 5001; PMI Feeds, Inc., Brentwood, MO, USA) and tap water were available ad libitum. All procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH
Pattern of innervation by axons expressing alpha-synuclein
Throughout the stomach and proximal duodenum, axons immunoreactive for alpha-synuclein were so densely distributed that the myenteric plexus was clearly delineated (Fig. 1). Large numbers of labeled fibers filled the interganglionic connectives, including the secondary and tertiary interganglionic connectives of the primary plexus. Individual axons were identifiable within the densely stained plexus, and were typically smooth in appearance when running within the connectives. Upon entering the
Discussion
In view of the conspicuous, though incompletely understood, roles of alpha-synuclein in synucleinopathies, including notably Parkinson's disease (e.g. Trojanowski and Lee 2002, Marti et al 2003, Norris et al 2004), the present experiment was designed to examine the pattern of expression of the protein in the autonomic circuitry of the proximal gut. The results delineate an extensive and complex network of vagal preganglionic axons and myenteric postganglionic neurons positive for
Conclusion
In summary, then, virtually all vagal motor fibers innervating the myenteric plexus of the proximal GI tract express alpha-synuclein in their axons and terminals. The preganglionic endings encircle and form appositions with myenteric postganglionic neurons, including those that express alpha-synuclein. The pathway of alpha-synuclein-positive vagal preganglionics that form appositions on postganglionic neurons that also express the protein satisfies the Braak proposal of a direct
Acknowledgments
We thank Michelle Murphy for her help with the SlideBook software, and Nazim Anwar for his expert assistance with the preparation of the medullas for FluoroGold analysis. This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIH DK61317 and DK27627).
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